TRD1 Project Summary The broad mission of our Center for Advanced Imaging Innovation and Research (CAI2R) is to bring together collaborative translational research teams for the development of high-impact biomedical imaging technologies, with the ultimate goal of changing day-to-day clinical practice. Technology Research and Development (TR&D) Project 1 aims to replace traditional complex and inefficient imaging protocols with simple, comprehensive acquisitions that also yield quantitative parameters sensitive to specific disease processes. In the first funding period of this P41 Center, our project team led the way in establishing rapid, continuous, comprehensive imaging methods, which are now available on a growing number of commercial magnetic resonance imaging (MRI) scanners worldwide. This foundation will allow us, in the proposed research plan for the next period, to enrich our data streams, to advance the extraction of actionable information from those data streams, and to feed the resulting information back into the design of our acquisition software and hardware. Thanks to developments during our first funding period, we are now in a position to question long-established assumptions about scanner design, originating from the classical imaging pipeline of human radiologists interpreting multiple series of qualitative images. We will reimagine the process of MR scanning, leveraging our core expertise in pulse-sequence design, parallel imaging, compressed sensing, model-based image reconstruction and machine learning. We will also extend our methods to complex multifaceted data streams, arising not only from MRI but also from Positron Emission Tomography (PET) and other imaging modalities, as well as from diverse arrays of complementary sensors.